The goal of this research is to understand the role of serotonin in female sexual behavior. The PI's previous work has focussed on identification of neural sites for the action of specific 5HT receptor subtypes involved in the mediation of the lordosis response. She has identified the VMN as a site for 5HT action and has shown that 5HT1A and 5HT2A/2C receptor subtypes respectively inhibit and facilitate lordosis. The current proposal will continue this line of inquiry, focussing on the idea that 5HT has dual effects on lordosis, and that these two receptor subtypes, 5HT1A and 5HT2A/2C, act in concert to modulate receptivity. The PI has hypothesized that it is the activation of 5HT1A sites in the VMN that are attenuated on proestrus, and the 5HT2A/2C receptor activation attenuates the lordosis-inhibiting effects of 5HT1A receptors. She has developed several testable predictions from this hypothesis. Some of these have already been tested and are reported in the preliminary data section. The others make up the body of this proposal. The revised application has seven aims. The first three aims involve testing the effects of various 5HT1A and 5HT2A/2C agonists and antagonists in the suboptimally hormone-primed ovariectomized rat to get at the generality of these dual serotonergic effects. The last four aims are designed to investigate the mechanism by which 5HT1A receptor agonists inhibit lordosis and 5HT2A/2C agonists facilitate lordosis. The two mechanisms to be tested are G-protein coupling to adenylyl cyclase and G-protein coupling to K+ channels. These choices are based on reports that agents which inhibit adenylyl cyclase inhibit lordosis while agents which facilitate the phosphoinositide system facilitate lordosis.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD028419-06
Application #
2403247
Study Section
Special Emphasis Panel (ZRG1-BPO (02))
Project Start
1991-08-01
Project End
1999-04-30
Budget Start
1997-05-01
Budget End
1998-04-30
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Texas Woman's University
Department
Biology
Type
Schools of Arts and Sciences
DUNS #
068979848
City
Denton
State
TX
Country
United States
Zip Code
76201
Uphouse, Lynda; Hiegel, Cindy; Martinez, Giovanny et al. (2015) Repeated estradiol benzoate treatment protects against the lordosis-inhibitory effects of restraint and prevents effects of the antiprogestin, RU486. Pharmacol Biochem Behav 137:1-6
Uphouse, Lynda; Pinkston, Jonathan; Baade, Duane et al. (2015) Use of an operant paradigm for the study of antidepressant-induced sexual dysfunction. Behav Pharmacol 26:697-705
Uphouse, Lynda (2015) Dose-dependent effects of the antiprogestin, RU486, on sexual behavior of naturally cycling Fischer rats. Behav Brain Res 282:95-102
Uphouse, Lynda; Hiegel, Cindy (2014) Allopregnanolone's attenuation of the lordosis-inhibiting effects of restraint is blocked by the antiprogestin, CDB-4124. Pharmacol Biochem Behav 122:16-9
Uphouse, Lynda (2014) Pharmacology of serotonin and female sexual behavior. Pharmacol Biochem Behav 121:31-42
Uphouse, Lynda; Hiegel, Cindy; Adams, Sarah et al. (2014) Prior hormonal treatment, but not sexual experience, reduces the negative effects of restraint on female sexual behavior. Behav Brain Res 259:35-40
Uphouse, Lynda; Hiegel, Cindy (2013) An antiprogestin, CDB4124, blocks progesterone's attenuation of the negative effects of a mild stress on sexual behavior. Behav Brain Res 240:21-5
Miryala, Chandra Suma Johnson; Hiegel, Cindy; Uphouse, Lynda (2013) Comparison of female Fischer and Sprague-Dawley rats in the response to ketanserin. Pharmacol Biochem Behav 114-115:52-7
Uphouse, Lynda; Adams, Sarah; Miryala, Chandra Suma Johnson et al. (2013) RU486 blocks effects of allopregnanolone on the response to restraint stress. Pharmacol Biochem Behav 103:568-72
Miryala, Chandra Suma J; Hiegel, Cindy; Uphouse, Lynda (2013) Sprague-Dawley and Fischer female rats differ in acute effects of fluoxetine on sexual behavior. J Sex Med 10:350-61

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